Vaccination Upregulates Th1 Cytokines in the Lung of Pigs Experimentally Infected with Mycoplasma hyopneumoniae

SIMPLE SUMMARY: Mycoplasma hyopneumoniae (Mhy) is the cause of porcine enzootic pneumonia (PEN) which, although not lethal, may lead to fatal pneumonia caused by opportunistic bacteria and/or viruses, in concurrence with environmental and management stressors due to reduced muco-ciliary clearance and impaired immune-inflammatory function. PEN spreads progressively with high morbidity rate, causing major economic losses to pig producers worldwide, associated to diminished production indexes and increased control costs, based on vaccination and antimicrobial treatments, used to mitigate those detrimental effects. Vaccination is commonly used for Mhy prophylaxis. While vaccines improve growth performance and reduce clinical signs and lung lesions, the results are often variable. In response to multiple stimuli, cytokines -molecular signals produced by a variety of immuno-modulatory cells- are involved in numerous protective biological activities. To investigate the role of cytokines in vaccinated and non-vaccinated pigs, an experimental model of infection was developed, by combining trans-tracheal and aerosol route, using a mixture of Mhy-field strains. Comparison of clinical, microbiological, pathological, and immunohistochemical parameters revealed significant differences depending upon the profile of cytokines expressed. These results indicate the importance to enhance Th1-type cytokine response—cell-mediated immunity -, to improve the effectiveness of Mhy-immunization, and to develop more efficient vaccines against PEN. ABSTRACT: Mycoplasma hyopneumoniae (Mhy) is the causative agent of enzootic pneumonia, characterized by high morbidity and low mortality rates in intensive swine production systems. To better understand the mechanisms underlying the protection of an inactivated whole cell vaccine, we investigated the immunohistochemical differences in the cytokine expression in vaccinated and non-vaccinated pigs experimentally infected with Mhy. Four-week-old Mhy-negative pigs (n = 24) were allocated to negative control (n = 8), or one of two Mhy-infected groups: vaccinated (n = 8) and non-vaccinated (n = 8). Infection was carried out by a combination of trans-tracheal and aerosol route. Lung samples were processed for histopathological and immunohistochemical studies, by using antibodies against Mhy, IL1-α, IL1-β, IL-2, IL-4, IL-5, IL-6, Il-8, IL-10, IL-12p35, IL-13, IL-17A, TNF-α, IFN-γ, and CD-4 lymphocytes. Although all cytokines increased in both infected groups, IL-2, IL-12, and IFN-γ were significantly overexpressed in vaccinated pigs. These findings, in conjunction with the decrease of macroscopic and histological lesions in vaccinated animals, indicate the importance to enhance Th1 response in the immunization strategies to control Mhy infection.